Typhoid fever is one of the infectious diseases caused by Salmonella enterica var. Typhi, which is a type of salmonella bacteria; infection being caused by the ingestion of contaminated drinking water, food, or the like. Typhoid fever is prevalent all over the world, particularly, in areas of Asia, Middle East, Eastern Europe, Africa, and Central and South America. Annually, 16 million people are affected by typhoid fever, and 0.6 million people die of this disease. Most of those killed are infants in developing countries. Currently, an attenuated salmonella bacterium (Ty21a) or the like is orally administered as a vaccine against typhoid fever caused by salmonella bacteria, but it cannot be administered to infants aged 5 or younger due to its side effects, such as diarrhea or vomiting. Once a person is affected by typhoid fever, an antibody against typhoid fever is developed inside the body, and immunity is acquired, but this effect does not last long.
Cholera is one of the infectious diseases caused by Vibrio cholerae O1 or O139. Cholera is prevalent all over the world, particularly, in Asia, Middle East, and Africa. Classical cholera epidemics repeatedly have occurred many times, and several million people have died of this disease due to its strong pathogenicity (death rate 20%). Currently, people are inoculated against this disease, but the effect of such inoculation is relatively low and said to be approximately 50%.
Bacterial dysentery (Shigellosis) is a bacterial infectious disease widely distributed throughout the world, and seen particularly in countries with poor hygiene. Bacterial dysentery is caused by intestinal bacteria belonging to the genus Shigella, which includes four groups consisting of Shigella dysenteriae, S. flexneri, S. boydii, and S. sonnei, in order of pathogenicity.
As described above, there are various bacterial infectious diseases, and it is clear that effective vaccines against bacterial infectious diseases are necessary. In particular, vaccines for preventing infectious diseases transmitted between humans are necessary. Currently, for example, some vaccines against various salmonella species are commercially available. These vaccines are sometimes effective, but have severe disadvantages. These vaccines typically induce antibodies as caused by infection with wild type bacteria, and an excessive load is placed on subjects.
In order to solve this problem, a study focused on the flagellum of bacteria has also been carried out. A flagellum is a long structure projecting from the cell surface of bacteria, and plays an important role when the cell moves and invades a host cell. The flagellum is comprised of a protein referred to as flagellin. This flagellin protein has been known to induce a high-level of antibodies. The antigenic protein flagellin of Salmonella typhimurium is described by McClelland M. et al. in Nature, vol. 413, p. 852 (2001). The antigenic protein flagellin of Vibrio cholerae is described by Heiderberg et al. in Nature, vol. 406, p. 477 (2000). Furthermore, the antigenic protein flagellin of Shigella dysenteriae is described by Tominaga A. et al. in Genes Genet. Syst., vol. 76, p. 111 (2001). However, an effective vaccine using this sort of antibody against flagellum has not been provided yet.